Article
Neurosciences
Hristo Varbanov, Shaobo Jia, Gaga Kochlamazashvili, Subhrajit Bhattacharya, Manal Ali Buabeid, Mohamed El Tabbal, Hussam Hayani, Stoyan Stoyanov, Weilun Sun, Hauke Thiesler, Iris Roeckle, Herbert Hildebrandt, Oleg Senkov, Vishnu Suppiramaniam, Rita Gerardy-Schahn, Alexander Dityatev
Summary: Dysregulated cortical expression of NCAM and deficits of its associated polySia are found in Alzheimer's disease and schizophrenia. Acute enzymatic removal of polySia in the prefrontal cortex leads to increased transmission mediated by GluN1/GluN2B NMDARs, impaired LTP, and increased tonic currents. Treatment with polySia fragments or inhibition of GluN1/GluN2B receptors restores LTP and cognitive tasks in polySia-deficient mice and Alzheimer's disease models. The data highlight the crucial role of polySia-NCAM in balancing signaling through synaptic/extrasynaptic NMDARs and the therapeutic potential of polySia fragments.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Neurosciences
Madeleine Kyrke-Smith, Lenora J. Volk, Samuel F. Cooke, Mark F. Bear, Richard L. Huganir, Jason D. Shepherd
Summary: Research shows that mice lacking the Arc gene do not exhibit deficits in hippocampal long-term potentiation (LTP), indicating that Arc is not necessary for LTP in the hippocampus.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Neurosciences
Karl Peter Giese
Summary: Autophosphorylation of calcium/calmodulin-dependent kinase II (CaMKII) plays a critical role in synaptic potentiation by allowing kinase signaling to outlast NMDA receptor-dependent calcium influx. However, the role of CaMKII is conditional, depending on the developmental stage and location of the synapse.
Article
Biochemistry & Molecular Biology
Abdallah Ahnaou, Kobe Heleven, Ria Biermans, Nikolay Manyakov, Wilhelmus H. Drinkenburg
Summary: This study highlights the importance of NMDAR in LTP synaptic plasticity, but specific blockade of the NR2B subunit does not alter hippocampal LTP. Pharmacokinetics at the doses used may have contributed to the lack of effects with specific antagonists.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Margarita Anisimova, Bas van Bommel, Rui Wang, Marina Mikhaylova, Joern Simon Wiegert, Thomas G. Oertner, Christine E. Gee
Summary: The study uses optogenetic stimulation to induce STDP and observes timing-dependent depression and potentiation. This study does not require electrodes and results suggest that synaptic depression after anticausal activation is a transient phenomenon.
Article
Cell Biology
Maria Andres-Alonso, Maximilian Borgmeyer, Hadi Mirzapourdelavar, Jakob Lormann, Kim Klein, Michaela Schweizer, Sabine Hoffmeister-Ullerich, Anja M. Oelschlegel, Alexander Dityatev, Michael R. Kreutz
Summary: The complex structure of neurons presents challenges for the maturation of synaptic membrane proteins. Golgi-satellites (GSs) are distributed along dendrites and can perform mature glycosylation, particularly sialylation. GSs polysialylate locally secreted NCAM, and their reduction leads to decreased levels of PSA-NCAM in distal dendrites and impaired long-term potentiation.
Article
Neurosciences
Tonghui Su, Yi Lu, Chaoying Fu, Yang Geng, Yelin Chen
Summary: This study demonstrates that the loss of GluN2A in adult mouse brains can elicit strong antidepressant-like responses without causing psychomimetic effects similar to Ketamine. The antidepressant effects of Ketamine and MK-801 are mainly mediated by the suppression of GluN2A rather than GluN2B.
NATURE NEUROSCIENCE
(2023)
Article
Neurosciences
Tonghui Su, Yi Lu, Chaoying Fu, Yang Geng, Yelin Chen
Summary: The study found that the loss of GluN2A in adult mice elicits antidepressant-like responses without causing psychomimetic effects similar to ketamine. The antidepressant effects of ketamine and MK-801 are mediated by the suppression of GluN2A, not GluN2B. Additionally, these drugs increase the excitability of hippocampal neurons through GluN2A.
NATURE NEUROSCIENCE
(2023)
Article
Pharmacology & Pharmacy
Wonseok Chang, Jihua An, Geun Hee Seol, Seung Ho Han, Jaeyong Yee, Sun Seek Min
Summary: Trans-anethole has neuroprotective effects and can positively influence synaptic plasticity, which suggests its potential for improving cognitive impairment caused by neurodegenerative diseases.
Article
Neurosciences
Gholam Hossein Meftahi, Mahnaz Bayat, Amir Hossein Zarifkar, Somaye Akbari, Afshin Borhani Haghighi, Maryam Naseh, Amirhossein Yousefi Nejad, Masoud Haghani
Summary: The study aimed to investigate the effects of edaravone administration on cellular and electrophysiological properties in a rat model of vascular dementia induced by bilateral carotid artery occlusion. The results showed that vascular dementia led to increased MDA levels, neuronal loss, reduced hippocampal volume, and impaired synaptic plasticity and memory function. However, treatment with edaravone decreased MDA levels, prevented neuronal loss and hippocampal volume reduction, improved synaptic plasticity and memory function.
BRAIN RESEARCH BULLETIN
(2021)
Article
Neurosciences
L. Fester, Gabriele M. Rune
Summary: Hippocampal neurons have the ability to synthesize sex steroids from cholesterol, with estradiol and testosterone playing important roles in maintaining synaptic transmission and connectivity. The synthesis of these steroids is regulated by internal and external factors, and there are sex-specific differences in how estradiol and dihydrotestosterone affect synaptic functions. The link between GnRH-induced estradiol synthesis and cyclical changes in spine density in the female hippocampus suggests a complex interaction between the hypothalamus and hippocampus in regulating neuronal responses to sex neurosteroids.
NEUROSCIENCE LETTERS
(2021)
Article
Neurosciences
Shikha Kalotra, Gurcharan Kaur
Summary: The study found that 5-NOT may serve as a potential neuroprotective candidate by promoting axonal growth and migration of neurons, as well as regulating the expression of synaptic plasticity and cell survival pathway proteins.
Article
Cell Biology
Wenhui Yan, Tingli Guo, Na Liu, Xin Cui, Xiaotong Wei, Yuzhuo Sun, Hao Hu, Lina Chen
Summary: Recent studies have demonstrated that EPO exerts neuroprotective and neurotrophic effects on neurological disorders. However, the potential benefits of EPO on diabetic cognitive impairments have not been well studied. In this research, the authors investigated the effects of EPO on diabetic mice and HT22 cells. They found that EPO treatment improved cognitive impairments, lowered blood glucose levels, and alleviated damage in both the pancreas and hippocampus. EPO also regulated the expression of various factors related to cell survival and apoptosis in HT22 cells. The findings suggest that EPO plays a protective role in diabetic cognitive impairments by modulating BDNF and PSD-95 expression via NMDA receptors.
CELLULAR SIGNALLING
(2023)
Article
Biochemistry & Molecular Biology
Daniel B. Dorman, Kim T. Blackwell
Summary: Synaptic plasticity, the experience-induced change in connections between neurons, plays a crucial role in learning and memory. This study investigates how spatiotemporal synaptic input patterns produce plasticity under in vivo-like conditions. The findings reveal the robustness of plasticity to trial-to-trial variability of spike timing and derive general rules describing the control of plasticity by spatiotemporal patterns of synaptic inputs.
Article
Biochemistry & Molecular Biology
Irene Sanchez-Rodriguez, Sara Temprano-Carazo, Danko Jeremic, Jose Maria Delgado-Garcia, Agnes Gruart, Juan D. Navarro-Lopez, Lydia Jimenez-Diaz
Summary: Synaptic plasticity is a cellular process involved in learning and memory, which adapts the synaptic strength and efficacy of neural transmission. The induction of synaptic plasticity is regulated by the balance between excitatory and inhibitory synaptic transmission. Limited studies have been done on long-lasting synaptic modifications during memory formation in freely moving animals. This study recorded field postsynaptic potentials in freely moving mice during an object recognition task and found that the synaptic plasticity of specific synapses in the dorsal hippocampus was enhanced when exploring novel objects.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Neurosciences
Philipp Ulbrich, Mahsima Khoshneviszadeh, Solveig Jandke, Stefanie Schreiber, Alexander Dityatev
Summary: This article discusses the common complex mechanisms of various neurological and psychiatric diseases such as vascular damage, CNS injury, epilepsy, depression, multiple sclerosis, and cerebral small vessel disease. It also explores translational strategies to advance the development of new therapies for these conditions.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2021)
Article
Neurosciences
Stoyan Stoyanov, Weilun Sun, Henning Peter Duesedau, Carla Cangalaya, Ilseob Choi, Hadi Mirzapourdelavar, David Baidoe-Ansah, Rahul Kaushik, Jens Neumann, Ildiko Rita Dunay, Alexander Dityatev
Summary: This study found that in the early stages of AD, the migration of microglia and myeloid cells is altered and can be partially restored by attenuation of the extracellular matrix (ECM). Enzymatic digestion of ECM by chondroitinase ABC (ChABC) ameliorated the defect in migration, indicating the crucial role of ECM in regulating cell migration in the brain.
Review
Neurosciences
Josephine Labus, Kian-Fritz Roehrs, Jana Ackmann, Hristo Varbanov, Franziska E. Mueller, Shaobo Jia, Kathrin Jahreis, Anna-Lena Vollbrecht, Malte Butzlaff, Yvonne Schill, Daria Guseva, Katrin Boehm, Rahul Kaushik, Monika Bijata, Philippe Marin, Severine Chaumont-Dubel, Andre Zeug, Alexander Dityatev, Evgeni Ponimaskin
Summary: Tauopathies are a group of neurodegenerative diseases characterized by the buildup of hyperphosphorylated Tau protein. This study reveals the important role of 5-HT7R/CDK5 signaling in Tauopathy, suggesting that targeting 5-HT7R could be a promising therapeutic strategy for Tauopathies. Preventing Tau hyperphosphorylation and neurotoxicity by blocking constitutive 5-HT7R activity highlights a potential treatment approach for Tau-related disorders.
PROGRESS IN NEUROBIOLOGY
(2021)
Article
Medicine, Research & Experimental
Diede W. M. Broekaart, Alexandra Bertran, Shaobo Jia, Anatoly Korotkov, Oleg Senkov, Anika Bongaarts, James D. Mills, Jasper J. Anink, Jesus Seco, Johannes C. Baayen, Sander Idema, Elodie Chabrol, Albert J. Becker, Wytse J. Wadman, Teresa Tarrago, Jan A. Gorter, Eleonora Aronica, Roger Prades, Alexander Dityatev, Erwin A. van Vliet
Summary: Research has shown that the expression of MMPs and TIMPs is persistently dysregulated in the hippocampus of patients with epilepsy and experimental animals. Treatment with the MMP2/9 inhibitor IPR-179 can reduce seizure severity and improve cognitive behavior in rodent models of epilepsy. It also prevents an MMP2/9-dependent switch-off that normally restrains network excitability, suggesting potential for further investigation in clinical trials.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Neurosciences
Alessandro Dario Confettura, Eleonora Cuboni, Mohamed Rafeet Ammar, Shaobo Jia, Guilherme M. Gomes, PingAn Yuanxiang, Rajeev Raman, Tingting Li, Katarzyna M. Grochowska, Robert Ahrends, Anna Karpova, Alexander Dityatev, Michael R. Kreutz
Summary: This study reveals that synaptic insulin resistance is induced through neddylation and activation of cullin-RING ligase complexes, which leads to ubiquitylation and degradation of the insulin-receptor substrate IRS1. Inhibition of neddylation can protect synaptic insulin signaling and improve memory deficits. These findings uncover the connection between high amyloid load, neuroinflammation, synaptic insulin resistance, and cognitive decline as well as impaired synaptic plasticity in high-risk aging.
TRANSLATIONAL NEURODEGENERATION
(2022)
Article
Cell Biology
David Baidoe-Ansah, Sadman Sakib, Shaobo Jia, Hadi Mirzapourdelavar, Luisa Strackeljan, Andre Fischer, Stepan Aleshin, Rahul Kaushik, Alexander Dityatev
Summary: Understanding the changes in ECM-related gene expression during aging and their impact on synaptic and cognitive functions provides valuable insights. This study found that ECM gene expression is downregulated in the hippocampus of aged mice, despite the accumulation of ECM proteoglycans. A key downregulated gene is Chst3, and its decreased expression is associated with reduced H3K4me3 methylation. The changes in ECM-related genes are accompanied by age-related cognitive decline, and there are differential effects of these genes on different cognitive tasks.
Article
Immunology
Carla Cangalaya, Susanne Wegmann, Weilun Sun, Lisa Diez, Anna Gottfried, Karin Richter, Stoyan Stoyanov, Janelle Pakan, Klaus-Dieter Fischer, Alexander Dityatev
Summary: Remodeling of synapses by microglia is critical for synaptic plasticity in the brain. In neuro-inflammation and neurodegenerative diseases, microglia can cause excessive synaptic loss, and this study investigated the underlying mechanisms by observing microglia-synapse interactions under inflammatory conditions. The findings showed that inflammatory stimuli prolonged microglia-neuron contacts, decreased surveillance of synapses, and promoted synaptic remodeling through the elimination of spines tagged by synaptic filopodia.
BRAIN BEHAVIOR AND IMMUNITY
(2023)
Article
Biochemistry & Molecular Biology
Maura Ferrer-Ferrer, Shaobo Jia, Rahul Kaushik, Jenny Schneeberg, Izabela Figiel, Stepan Aleshin, Andrey Mironov, Motahareh Safari, Renato Frischknecht, Jakub Wlodarczyk, Oleg Senkov, Alexander Dityatev
Summary: This study investigates the functional importance of neurotrypsin (NT) in synaptic plasticity, learning, and memory extinction. The results show that NT-deficient mice exhibit impaired long-term potentiation, contextual fear memory deficits, and sociability deficits. This highlights the crucial role of NT in synaptic formation and strengthening.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Neurosciences
Hristo Varbanov, Shaobo Jia, Gaga Kochlamazashvili, Subhrajit Bhattacharya, Manal Ali Buabeid, Mohamed El Tabbal, Hussam Hayani, Stoyan Stoyanov, Weilun Sun, Hauke Thiesler, Iris Roeckle, Herbert Hildebrandt, Oleg Senkov, Vishnu Suppiramaniam, Rita Gerardy-Schahn, Alexander Dityatev
Summary: Dysregulated cortical expression of NCAM and deficits of its associated polySia are found in Alzheimer's disease and schizophrenia. Acute enzymatic removal of polySia in the prefrontal cortex leads to increased transmission mediated by GluN1/GluN2B NMDARs, impaired LTP, and increased tonic currents. Treatment with polySia fragments or inhibition of GluN1/GluN2B receptors restores LTP and cognitive tasks in polySia-deficient mice and Alzheimer's disease models. The data highlight the crucial role of polySia-NCAM in balancing signaling through synaptic/extrasynaptic NMDARs and the therapeutic potential of polySia fragments.
NEUROBIOLOGY OF DISEASE
(2023)
Review
Cell Biology
Stefanie Schreiber, Jose Bernal, Philipp Arndt, Frank Schreiber, Patrick Mueller, Lorena Morton, Ruediger Christian Braun-Dullaeus, Maria Del Carmen Valdes-Hernandez, Roberto Duarte, Joanna Marguerite Wardlaw, Sven Guenther Meuth, Grazia Mietzner, Stefan Vielhaber, Ildiko Rita Dunay, Alexander Dityatev, Solveig Jandke, Hendrik Mattern
Summary: Brain vascular health is crucial in preventing and slowing down the progression of amyotrophic lateral sclerosis (ALS). Impaired brain vascular health in ALS leads to decreased levels of vascular endothelial growth factor, compromised endothelial cell formation, and blood-brain barrier integrity. This review discusses the pathogenesis of impaired brain vascular health in ALS and the potential of novel magnetic resonance imaging techniques in its detection. It also highlights the importance of blood supply patterns to the motor cortex as a marker of resistance and resilience against vascular risk and events in ALS, providing insights for ALS management and understanding of the disease.
Article
Cell Biology
Inseon Song, Tatiana Kuznetsova, David Baidoe-Ansah, Hadi Mirzapourdelavar, Oleg Senkov, Hussam Hayani, Andrey Mironov, Rahul Kaushik, Michael Druzin, Staffan Johansson, Alexander Dityatev
Summary: Our study showed that removing highly sulfated heparan sulfates with heparinase 1 impaired axonal excitability and reduced ankyrin G expression at the axon initial segments in the CA1 region of the hippocampus. In vivo delivery of heparinase 1 elevated CaMKII autophosphorylation 24 hours after injection, and it also induced context overgeneralization when delivered after contextual fear conditioning. Co-administration of heparinase 1 with the CaMKII inhibitor rescued neuronal excitability, ankyrin G expression, and context discrimination.
Article
Biology
Babak Saber Marouf, Antonio Reboreda, Frederik Theissen, Rahul Kaushik, Magdalena Sauvage, Alexander Dityatev, Motoharu Yoshida
Summary: The modulation of beta oscillations is believed to support memory encoding, and the TRPC4 channels play a role in this process. Beta oscillations are related to behavior and memory functions, and their ability to modulate beta and low-gamma oscillations is dependent on TRPC4 channels. These findings suggest that TRPC4 channels are crucial for the regulation of beta oscillations in the CA1 region.
Article
Cell Biology
Priyanka D. Pinky, Jenna Bloemer, Warren D. Smith, Yifeng Du, Ryan T. Heslin, Sharay E. Setti, Jeremiah C. Pfitzer, Kawsar Chowdhury, Hao Hong, Subhrajit Bhattacharya, Muralikrishnan Dhanasekaran, Alexander Dityatev, Miranda N. Reed, Vishnu Suppiramaniam
Summary: Cannabis use during pregnancy is a growing concern due to its potential impact on the neurofunctional and cognitive development of the offspring. This study investigates the mechanisms behind learning and memory deficits in adolescent rats exposed to prenatal cannabinoids. The findings suggest that prenatal cannabinoid exposure leads to hippocampal-dependent memory deficits, accompanied by altered synaptic plasticity and an imbalance in GluN2A- and GluN2B-mediated signaling. Furthermore, the study reveals that reduced expression of neural cell adhesion molecule (NCAM) and polysialylated-NCAM (PSA-NCAM) may contribute to the impaired synaptic plasticity. The administration of exogenous PSA mitigates the memory deficits, highlighting the potential therapeutic implications of manipulating the GluN2A- and GluN2B- signaling pathways.
Meeting Abstract
Peripheral Vascular Disease
Philipp Ulbrich, Lorena Morton, Michael Briese, Naomi Laemmlin, Hendrik Mattern, Mohammed Hasanuzzaman, Melina Westhues, Cornelia Garz, Axel Becker, Alexander Dityatev, Solveig Jandke, Deniz Yilmazer-Hanke, Michael Sendtner, Ildiko Dunay, Stefanie Schreiber
JOURNAL OF HYPERTENSION
(2022)
Meeting Abstract
Peripheral Vascular Disease
Philipp Ulbrich, Lorena Morton, Michael Briese, Naomi Laemmlin, Hendrik Mattern, Mohammed Hasanuzzaman, Melina Westhues, Cornelia Garz, Axel Becker, Alexander Dityatev, Solveig Jandke, Deniz Yilmazer-Hanke, Michael Sendtner, Ildiko Dunay, Stefanie Schreiber
JOURNAL OF HYPERTENSION
(2022)
